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| Home > Publications database > $^{18}$F-Markierung hochaffiner all-D-Peptide zur $in \ vivo$ Diagnostik von $\beta$-Amyloid-Plaques |
| Home > Publications database > $^{18}$F-Markierung hochaffiner all-D-Peptide zur $in \ vivo$ Diagnostik von $\beta$-Amyloid-Plaques |
| Book/Report/Dissertation / PhD Thesis | FZJ-2015-05026 |
2015
Forschungszentrum Jülich GmbH Zentralbibliothek, Verlag
Jülich
Please use a persistent id in citations: http://hdl.handle.net/2128/9007
Report No.: Juel-4388
Abstract: For the Development of new selective radiotracers which can be used for $\textit{in vivo}$ imaging of $\beta$-Amyloid plaques in the context of Alzerheimer’s Disease by positron-emission-tomography this study aimed at the application of various strategies for $^{18}$F-labelling of the all-d peptide D3 (sequence: RPRTRLHTHRNR). In previous reports D3 showed promising results for the affinity to $\beta$-Amyloid. The labelling reaction with acylation agents required an extension of the original peptide with a lysine residue at the C-terminus. The prosthetic group succinimidyl-4-[$^{18}$F]fluorobenzoate could be produced with a radiochemical yield of 41 - 60 %. While conjugation with various model compounds gave good results the coupling with the D3-derivative was not possible.Through the extension of D3 with cysteine instead of lysine it was possible touse thiol-reactive prosthetic groups. For this 4-[$^{18}$F]fluorobenzylmaleimide was preparedby two different synthetic routes. But neither one of them lead to a radiochemicalyield above 5% so further use was neglected. The preparation of 1-[3-(2-[$^{18}$F]fluoropyridine-3-oxyl)propyl]pyrrol-2,5-dione succeeded by a three-step radiosynthesis within 110 minutes and lead to a radiochemical of 2-20 %. The development of a new strategy via the protection of the maleimide function allowed toperform the radiosynthesis in only two steps within 60 minutes and an overall radiochemicalyield of about 20 ± 5%. The following coupling with the all-d peptidecould be done with yields of about 95% within 15 minutes. This, the synthesis ofthe radiofluorinated D3-derivative including all purification steps could be achievedwithin 120 minutes.The successfully $^{18}$F-labelled D3-derivative was used for further preclinical $\textit{in vitro}$investigation by performing autoradiography of mouse brain slices which expressed$\beta$-Amyloid plaques. Optimisation of the parameters of incubation were done in orderto reduce the affinity of the compounds to the glass surface. It could be determinedthat the l-enantiomer of the radiofluorinated D3-derivative showed no affinity to thetissue. However the all-d peptide showed an increased uptake at some tissue regionswith enrichment of $\beta$-Amyloid.
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